Integrated transcriptomic, phenotypic, and functional study reveals tissue‐specific immune properties of mesenchymal stromal cells

Clinical‐grade mesenchymal stromal cells (MSCs) can be expanded from bone marrow and adipose tissue to treat inflammatory diseases and degenerative disorders. However, the influence of their tissue of origin on their functional properties, including their immunosuppressive activity, remains unsolved. In this study, we produced paired bone marrow‐derived mesenchymal stromal cell (BM‐MSC) and adipose‐derived stromal cell (ASC) batches from 14 healthy donors. We then compared them using transcriptomic, phenotypic, and functional analyses and validated our results on purified native MSCs to infer which differences were really endowed by tissue of origin. Cultured MSCs segregated together owing to their tissue of origin based on their gene expression profile analyzed using differential expression and weighted gene coexpression network analysis. This translated into distinct immune‐related gene signatures, phenotypes, and functional cell interactions. Importantly, sorted native BM‐MSCs and ASCs essentially displayed the same distinctive patterns than their in vitro‐expanded counterparts. As a whole, ASCs exhibited an immune profile consistent with a stronger inhibition of immune response and a lower immunogenicity, supporting the use of adipose tissue as a valuable source for clinical applications. Clinical‐grade mesenchymal stromal cells (MSCs) derived from adipose tissue versus bone marrow display tissue‐imprinted gene expression profile, phenotype, and functional properties as highlighted by the comprehensive analysis of paired cultures MSC batches obtained from the same donors and the validation on native sorted MSCs.